Protein kinase A (PKA) integrates inputs from G-protein-coupled neuromodulator receptors to modulate synaptic and cellular function. Gαs signaling stimulates PKA activity, whereas Gαi inhibits PKA activity. Gαq, on the other hand, signals through phospholipase C, and it remains unclear whether Gαq-coupled receptors signal to PKA in their native context. Here, using two independent optical reporters of PKA activity in acute mouse hippocampus slices, we show that endogenous Gαq-coupled muscarinic acetylcholine receptors activate PKA. Mechanistically, this effect is mediated by parallel signaling via either calcium or protein kinase C. Furthermore, multiple Gαq-coupled receptors modulate phosphorylation by PKA, a classical Gαs/Gαi effector. Thus, these results highlight PKA as a biochemical integrator of three major types of GPCRs and necessitate reconsideration of classic models used to predict neuronal signaling in response to the large family of Gαq-coupled receptors.

中文翻译：

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内源性Gαq耦合神经调节剂受体激活蛋白激酶A

蛋白激酶A（PKA）整合了G蛋白偶联神经调节受体的输入，以调节突触和细胞功能。Gαs信号传导刺激PKA活性，而Gαi抑制PKA活性。另一方面，Gαq通过磷脂酶C发出信号，目前尚不清楚Gαq偶联受体是否在其天然背景下向PKA发出信号。在这里，使用急性小鼠海马切片中PKA活性的两个独立的光学报道分子，我们表明内源性Gαq偶联的毒蕈碱型乙酰胆碱受体可以激活PKA。从机理上讲，这种作用是通过钙或蛋白激酶C的平行信号介导的。此外，多个Gαq偶联受体通过经典的Gαs/Gαi效应子PKA调节磷酸化。因此，